Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

Abstract

SummaryThe first organocatalytic asymmetric synthesis of smyrindiol, by using an (S)-proline catalyzed enantioselective intramolecular aldol reaction as the key step, is described. Smyrindiol was synthesized from commercially available 2,4-dihydroxybenzaldehyde in 15 steps, with excellent stereoselectivity (de = 99%, ee = 99%). In the course of this total synthesis a new and mild coumarin assembly was developed.

Stereodivergent Synthesis of 3-Aminooxindole Derivatives Containing Vicinal Tetrasubstituted Stereocenters via the Mannich Reaction

“…Natural products such as avicenol A, smyrindiol, vaginidiol, and vaginol (Figure ) contain the 2.3-dihydrobenzofuran moiety.…”

Expedient Approach to 6‐Bromo‐2‐isopropylidenecoumaranone, a Potential Intermediate for the Synthesis of TMC‐120B, Pseudodeflectusin, and Their Congeners

“…To be successful, the reaction had to be conducted at temperatures below 40 °C, in order to avoid reduced yields due to the concomitant uncontrolled base‐catalyzed cyclization of the resulting acetonyl ether to afford alcohol 24 and its diasteromer 24a , and the generation of unwanted side products . Under these conditions, the yield of 23 was 82%.…”

“…278.9633). 1-[(2R*,3S*)-6-Bromo-2,3-dihydro-3-hydroxy-1-benzofuran-2-yl]ethanone(24). To a solution of 23 (500 mg, 1.95 mmol) in DMF (8.3 ml) was added H 2 O (0.035 ml, 1.95 mmol) and L-proline (44 mg, 0.39 mmol).…”

Asymmetric organocatalyzed synthesis of coumarin derivatives

“…Using a completely different strategy from the above discussed, in which the coumarin core was the starting material in the asymmetric organocatalyzed reaction, the Enders group described the use of ( S )-proline as catalyst in an intramolecular aldol reaction, enabling a new strategy to obtain coumarin natural products [ 34 ]. As for example, the total synthesis of (+)-smyrindiol ( 17 ), a linear dihydrofuranocoumarin isolated from the roots of Smyrniopsis aucheri , was developed [ 35 ]. The 5-enolexo aldol key step of this synthesis was performed using 40 mol % of ( S )-proline and the desired product 14 was obtained in good yield (71%), and high diastereo- and enantioselectivities ( Scheme 4 ).…”